Reduced baseline male fertility and increased sensitivity to hypoxic stress in high-elevation deer mice
Abstract
Extreme environments like high elevation impose chronic challenges to endothermic animals who must sustain metabolic demand despite reduced oxygen availability. Male reproduction is a tightly regulated physiological system, and hypoxia exposure has negative but transient effects on male reproductive output in diverse mammal species not adapted to high-elevation. Little is known about whether high elevation populations adapt to the detrimental effects of hypoxia on male reproductive physiology. Here, we use high- and low-elevation populations of deer mice (Peromyscus maniculatus) and a lowland congener, P. leucopus, to test how male reproductive phenotypes have diverged across populations and in response to hypoxia exposure across acute, intermediate, and chronic timescales. We complement these phenotypic assays with bulk RNA sequencing of testes to assess the testis-specific response to hypoxia. Contrary to expectations, hypoxia exposure had a negligible effect on low-elevation strains, while highland mice had both lower baseline fertility and heightened sensitivity to hypoxic stress including complete absence of mature sperm. Gene expression patterns indicate that hypoxia exposure dramatically reorganizes testes architecture in highland mice, consistent with testicular regression similar to that observed in seasonally breeding mammals. We hypothesize that this increased sensitivity of male reproductive physiology in highlanders reflects a life history trade-off, allowing energy reallocation between reproduction, survival, and thermogenesis in response to stress in extreme environments.
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BibTeX
@misc{hunnicutt2026reduced,
title = {{Reduced baseline male fertility and increased sensitivity to hypoxic stress in high-elevation deer mice}},
author = {Kelsie E. Hunnicutt and Emma S. Glenn and Joe C. Perry and Madison Q. Tatro and Lacey K. Conrad and Makenna Y. Juergens and Kathryn Wilsterman and Benjamin M. Skinner and Erica L. Larson and Jonathan P. Velotta},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759662},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759662v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Reduced baseline male fertility and increased sensitivity to hypoxic stress in high-elevation deer mice
AU - Kelsie E. Hunnicutt
AU - Emma S. Glenn
AU - Joe C. Perry
AU - Madison Q. Tatro
AU - Lacey K. Conrad
AU - Makenna Y. Juergens
AU - Kathryn Wilsterman
AU - Benjamin M. Skinner
AU - Erica L. Larson
AU - Jonathan P. Velotta
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759662
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759662v1
AB - Extreme environments like high elevation impose chronic challenges to endothermic animals who must sustain metabolic demand despite reduced oxygen availability. Male reproduction is a tightly regulated physiological system, and hypoxia exposure has negative but transient effects on male reproductive output in diverse mammal species not adapted to high-elevation. Little is known about whether high elevation populations adapt to the detrimental effects of hypoxia on male reproductive physiology. Here, we use high- and low-elevation populations of deer mice (Peromyscus maniculatus) and a lowland congener, P. leucopus, to test how male reproductive phenotypes have diverged across populations and in response to hypoxia exposure across acute, intermediate, and chronic timescales. We complement these phenotypic assays with bulk RNA sequencing of testes to assess the testis-specific response to hypoxia. Contrary to expectations, hypoxia exposure had a negligible effect on low-elevation strains, while highland mice had both lower baseline fertility and heightened sensitivity to hypoxic stress including complete absence of mature sperm. Gene expression patterns indicate that hypoxia exposure dramatically reorganizes testes architecture in highland mice, consistent with testicular regression similar to that observed in seasonally breeding mammals. We hypothesize that this increased sensitivity of male reproductive physiology in highlanders reflects a life history trade-off, allowing energy reallocation between reproduction, survival, and thermogenesis in response to stress in extreme environments.
SN - 2692-8205
ER -